Recruiting
Phase 1
Phase 2

Psilocybin

Sponsor:

Johns Hopkins University

Code:

NCT05301608

Conditions

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

Psilocybin

Placebo

Study Details

Brief summary:

This research study will use computerized tasks, electroencephalography (EEG), and magnetic resonance imaging (MRI) to look at how the drug psilocybin, a naturally occurring compound contained in hundreds of species of psychoactive mushrooms, changes thoughts and brain activity.

Conditions

Healthy

Study ID

NCT05301608

Start date

Mar 3, 2022

Status verified date

Jul, 2026

Completion date

Jan 1, 2027

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Inclusion Criteria:

  • 18 to 75 years old
  • Have given written informed consent
  • Have at least a high-school level of education or equivalent (e.g. GED) and be fluent in English
  • Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
  • Agree to consume approximately the same amount of caffeine-containing beverage (e.g. coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the morning of the drug session day. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on the session day.
  • Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine.
  • Agree not to take any "as-needed" medications on the mornings of drug sessions
  • Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
  • Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
  • Have used a psychedelic drug (e.g. lysergic acid diethylamide(LSD)/acid, psilocybin mushrooms, ayahuasca) at least five times in their lifetime.
  • Proof of COVID-19 vaccination

Exclusion Criteria:

  • Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
  • Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrilation), artificial heart valve, or heart attack in the past year
  • Epilepsy with history of seizures
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  • Currently taking psychoactive prescription medication on a regular (e.g. daily) basis
  • Currently taking on a regular (e.g. daily) basis any medications having a primary centrally-acting serotonergic effect, including mono-amine oxidase inhibitors (MAOIs). For individuals who have intermittent or "as needed" use of such medications, psilocybin sessions will not be conducted until at least five half-lives of the agent have elapsed after the last dose.
  • More than 20% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table
  • Current or past history of meeting Diagnostic and Statistical Manual, version 5 (DSM-5) criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition)
  • Current or past history within the last five years of meeting DSM-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)
  • Have a first or second-degree relative with bipolar I disorder, schizophrenia spectrum, or other psychotic disorders (except substance/medication-induced or due to another medical condition)
  • Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
  • Has history of migraine, tension, or other recurring headaches.
  • Head trauma, traumatic brain injury, or concussion with loss of consciousness for >2 minutes
  • Contraindications for magnetic resonance imaging (MRI) (e.g. claustrophobia incompatible with MRI scanning, medical device or implant incompatible with MRI, prior history as a metal worker and/or certain metallic objects in the body)
  • Left-handedness (assessed by the Edinburgh Handedness Inventory)

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Psilocybin First

Psilocybin (10mg) will be administered one time orally as a capsule taken with water. Expected duration of acute effects is approximately 6 hours. After a period of a washout, participants will switch to the placebo intervention.

placebo comparator: Placebo First

Participants will be administered placebo in a clinical setting. Placebo is administered orally as a capsule taken with water. After a period of a washout, participants will switch to the Psilocybin intervention.

Interventions

Psilocybin

The psilocybin used in this study is synthetically manufactured and formulated under current good manufacturing practices (cGMP). The active drug is encapsulated using a size 0 blue gelatin capsule and contains 10 mg of psilocybin.

Placebo

The placebo used in this study is microcrystalline cellulose, an inert substance, encapsulated using a size 0 blue gelatin capsule.

Primary outcome measure

  • Difference between drug conditions in the frequency of word use during free association tasks [ Time Frame: 8 weeks ]
  • Sensitivity in distinguishing old versus newly presented visual stimuli [ Time Frame: 8 weeks ]
  • Accuracy in the remote associates task as assessed by total correct number of trials [ Time Frame: 8-week study period ]
  • Accuracy in the alternative uses task [ Time Frame: 8-week study period ]
  • Alpha band power in EEG record [ Time Frame: 8-week study period ]
  • Reliability of whole-brain response while watching videos [ Time Frame: 8-week study period ]

Central Contacts and Locations

Central contacts

Gabi Lofland

(410) 550-2253gloflan1@jhmi.edu

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research

Recruiting

Baltimore, Maryland, United States, 21224

Contacts

Frederick S Barrett

410-550-9777fbarret2@jh.edu

More Information

Sponsor

Johns Hopkins University

Last update posted

Jul 23, 2026

Last verified

Jul, 2026

Keywords

  • psilocybin
  • electroencephalography (EEG)
  • magnetic resonance imaging (MRI)
  • creativity
  • cognition

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-07-23.